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Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target

Chin-Sheng Hung1,2,3, Sheng-Chao Wang4, Yi-Ting Yen5

  • 1Division of Breast Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan. hungcs@tmu.edu.tw.

International Journal of Molecular Sciences
|October 13, 2018
PubMed

Insights

CCND2 gene hypermethylation is common in lung and breast cancers, acting as a poor prognostic factor. The drug antroquinonol D upregulates CCND2, inhibiting cancer cell growth and migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lung and breast cancers are leading causes of mortality in women globally.
  • Precision medicine advances rely on identifying molecular alterations and targeted therapies.
  • CCND2 has emerged as a common molecular target in both lung and breast cancers.

Purpose of the Study:

  • To investigate the clinical significance of CCND2 alterations in lung and breast cancer.
  • To explore CCND2 as a potential diagnostic marker, prognostic factor, and drug target.
  • To evaluate the effect of antroquinonol D on CCND2 expression and cancer cell behavior.

Main Methods:

  • Genome-wide methylation analysis
  • Quantitative methylation-specific real-time PCR (Polymerase Chain Reaction)
  • Analysis of The Cancer Genome Atlas (TCGA) western cohort data
  • Cell model assays

Main Results:

  • CCND2 promoter hypermethylation was found in 40.9% of breast tumors and 44.4% of plasma cell-free DNA.
  • Hypermethylation of CCND2 was also observed in female lung cancer and breast cancer patients in the TCGA cohort.
  • CCND2 promoter hypermethylation independently predicted a poor prognosis.
  • CCND2 expression inhibited cancer cell growth and migration; antroquinonol D upregulated CCND2, induced cell cycle arrest, and inhibited cancer progression.

Conclusions:

  • CCND2 promoter hypermethylation serves as a potential diagnostic and prognostic biomarker for lung and breast cancers.
  • CCND2 represents a viable drug target for cancer therapy.
  • Antroquinonol D demonstrates potential as an agent to induce CCND2 expression and inhibit cancer progression.
Keywords:
Antrodia camphorataCCND2antroquinonol Dcirculating cell-free DNAhypermethylationlung adenocarcinomaprognostic factortriple-negative breast cancer (TNBC)tumor suppressor gene

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